The research project aims at studying the relation between antipsychotic efficacy and effects on brain catecholamine metabolism for a number of drugs empirically found to be effective in the treatment of schizophrenia. In animals the rate of synthesis of C14-labelled dopamine and noradrenaline formed from intravenously administered labelled phenylalanine and tyrosine are investigated. All antipsychotic drugs investigated so far including chlorpromazine, haloperidol and clozapine are potent stimulators of brain dopamine synthesis. Mass fragmentometric methods using deuterated compounds as internal standards for the estimation of homovanillic acid dihydroxy-phenylacetic acid, 3- methoxytyramine and dopamine were developed. These methods allow the estimation of these compounds in small tissue samples of the rat brain. Haloperidol increased HVA levels to a much greater extent in the corpus striatum than in limbic brain areas as the olfactory tubercle. Clozapine on the other side, an antipsychotic agent which lacks extrapyramidal side-effects, increased HVA levels to about the same extent in striatal and limbic brain areas. The results indicate that the antipsychotic efficacy of drugs is related to their tendency to accelerate dopamine synthesis in limbic brain areas. The current project aims at studying the relation between antipsychotic efficacy and effects on limbic brain dopamine synthesis.